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Biomedical subjects

S J Chew

Publications and source records attributed to S J Chew.

At least 37 records · Page 2Linked to original sources

Myopia in children born premature or with low birth weight.

PURPOSE: To evaluate the association of myopia or astigmatism in children without retinopathy of prematurity (ROP) born premature or with low birth weight. METHODS: This cross-sectional study was conducted in Singapore where 527 children from three kindergartens aged 2 to 7 years without a history of ROP were recruited. Information on birth weight and gestational age at birth was obtained from a personal booklet and the refractive error in spherical equivalents was measured using distance photoretinoscopy. The data was analysed with univariate analysis and logistic regression models. RESULTS: There was no difference in the prevalence of myopia in children born premature or with low birth weight. There was also no difference in astigmatism in children born premature or with low birth weight. CONCLUSION: This study shows no relationship between astigmatism or myopia with prematurity or low birth weight in children born without retinopathy of prematurity.

Astigmatism↗

Quantal duration of auditory memories.

Neuronal responses in the caudomedial neostriatum (NCM) of adult zebra finches (Taeniopygia guttata) decreased upon repeated, unreinforced presentations of conspecific song, calls, or other complex sounds. This "stimulus-specific habituation" is a form of learning, and its spontaneous loss, a form of "forgetting." Spontaneous forgetting occurred only at narrowly defined times (2 to 3, 6 to 7, 14 to 15, 17 to 18.5, 46 to 48, or 85 to 89 hours after first exposure to a stimulus), determined by stimulus class, number of presentations, and interval between presentations. The first five forgetting times coincided with periods when gene expression and protein synthesis in NCM were required for maintenance of the longer lasting (85 to 89 hours) habituation. The number of successive episodes of gene expression induced by a stimulus, but occurring long after stimulus presentation, appears to determine the quantal duration of auditory memories.

Acoustic Stimulation↗

A large-capacity memory system that recognizes the calls and songs of individual birds.

Auditory responses in the caudomedial neostriatum (NCM) of the zebra finch (Taeniopygia guttata) forebrain habituate to repeated presentations of a novel conspecific song. This habituation is long lasting and specific to individual stimuli. We here test the acoustic and ethological basis of this stimulus-specific habituation by recording extracellular multiunit activity in the NCM of awake male and female zebra finches presented with a variety of conspecific and heterospecific vocalizations, white noise, and tones. Initial responses to conspecific song and calls and to human speech were higher than responses to the other stimuli. Immediate habituation rates were high for all novel stimuli except tones, which habituated at a lower rate. Habituation to conspecific calls and songs outlasted habituation to other stimuli. The extent of immediate habituation induced by a particular novel song was not diminished when other conspecific songs were presented in alternation. In addition, the persistence of habituation was not diminished by exposure to other songs before testing, nor was it influenced by gender or laterality. Our results suggest that the NCM is specialized for remembering the calls and songs of many individual conspecifics.

Animals↗

Decrements in auditory responses to a repeated conspecific song are long-lasting and require two periods of protein synthesis in the songbird forebrain.

Earlier work showed that playbacks of conspecific song induce expression of the immediate early gene ZENK in the caudo-medial neostriatum (NCM) of awake male zebra finches and that this response disappears with repeated presentations of the same stimulus. In the present study, we investigated whether repetitions of a song stimulus also elicited a decrement in the electrophysiological responses in the NCM neurons of these birds. Multiunit auditory responses in NCM were initially vigorous, but their amplitude decreased (habituated) rapidly to repeated stimulation, declining to about 40% of the initial response during the first 50 iterations. A similar time course of change was seen at the single unit level. This habituation occurred specifically for each song presented but did not occur when pure tones were used as a stimulus. Habituation to conspecific, but not heterospecific, song was retained for 20 h or longer. Injections of inhibitors of protein or RNA synthesis at the recording site did not affect the initial habituation to a novel stimulus, but these drugs blocked the long-term habituation when injected at 0.5-3 h and at 5.5-7 h after the first exposure to the stimulus. Thus, at least two waves of gene induction appear to be necessary for long-lasting habituation to a particular song.

Acoustic Stimulation↗

Prevention of blinking alters iris configuration in pigment dispersion syndrome and in normal eyes.

PURPOSE: To examine the effect of blinking on iris configuration and aqueous humor distribution between the posterior and anterior chambers in eyes with pigment dispersion syndrome compared with healthy eyes. METHODS: High-resolution, anterior segment ultrasound biomicroscopy was performed on ten eyes of ten patients with untreated pigment dispersion syndrome and on ten control subjects. Patients were scanned continuously for 15 minutes or until the maximal change in iris configuration occurred. During this time, the eyelids were held open mechanically, and blinking was prevented. Eyes then were rescanned immediately after blinking. RESULTS: Initial iris configuration was concave in all eyes with pigment dispersion syndrome, whereas in control eyes it was concave in four eyes, planar in four eyes, and convex in two eyes. Iridozonular contact occurred in eyes with pigment dispersion syndrome only. Iridolenticular contact was greater in eyes with pigment dispersion syndrome than in control eyes. Analysis of covariance controlling for age, sex, and refractive error showed pigment dispersion syndrome to be a significant predictor of increased iris concavity. During continuous scanning, the mean change in iris position, from most concave to most convex, and mean time to the maximal change in iris configuration were greater for eyes with pigment dispersion syndrome than in control eyes and were related to the degree of initial iris concavity only (analysis of covariance). In six eyes with pigment dispersion syndrome, the eye cup was removed, normal blinking was permitted, and the eye was rescanned. The iris resumed a concave configuration in all eyes. CONCLUSION: Increased iris concavity in pigment dispersion syndrome appears to be related to increased iridolenticular contact. This creates an anatomic configuration that predisposes to reverse pupillary block. The accumulation of aqueous humor in the posterior chamber, when blinking is prevented, alters iris position in pigment dispersion syndrome and in healthy eyes and increases iridozonular and iridociliary-process distances while minimizing iridolenticular contact. Normal blinking appears to create transient vector forces which promote aqueous humor flow from the posterior to anterior chamber.

Adult↗

Cell cycle kinetics in pterygium at three latitudes.

The cell cycle kinetics of 93 specimens of pterygial tissue, as well as 19 specimens of normal conjunctiva, from patients at three sites representing three different latitudes (Singapore, 1 degree; Hong Kong, 22 degrees; and Little Rock, Arkansas, 34 degrees) were evaluated by flow cytometry. The results showed no difference in cellular proliferation patterns between pterygial and conjunctival tissue at any of the sites, suggesting that pterygium is not a disorder of excess cellular proliferation. Transmission electron microscopy showed extracellular matrix to be a prominent component of pterygium. Cellular proliferation patterns of primary and recurrent pterygium were not significantly different from each other. Factors associated with increased incidence of pterygium included male sex, outdoor occupation, and advanced age.

Adult↗

Confocal microscopy of corneal graft rejection.

Corneal allografts were transplanted into inflamed and vascularized graft beds in rabbit eyes. The grafts were examined every 4 days by slit-lamp biomicroscopy and scanning confocal microscopy. Confocal images were recorded with a video camera and computer enhanced in real-time. Layers of the cornea were visualized in serial optical sections parallel to the epithelium. In the third postoperative week, signs of graft rejection were observed; slit-lamp examination revealed a circumferential line of epithelial rejection, along with cloudiness and edema. Vessels were observed growing into the graft. By confocal microscopy, infiltrating cells were seen in the graft stroma. Foci of cells were especially pronounced around the sutures. Scattered leukocyte infiltrates were prominent at capillary terminals. There was an accompanying reduction in the stromal keratocyte density in the region of the infiltrate. Additionally, various degrees of fibrosis were noted around each suture and at the host-graft interface. Confocal microscopy may provide a valuable clinical tool for determining the earliest indicators of an antigraft immune response, and as an aid in the differential diagnosis of other inflammatory conditions of the cornea.

Animals↗

In vivo confocal microscopy of corneal wound healing after excimer laser photorefractive keratectomy.

We used real-time scanning confocal microscopy to evaluate early changes in corneal wound healing after excimer laser photorefractive keratectomy (PRK). Adult New Zealand White rabbits were given photorefractive keratectomy treatments appropriate for 5.00 to 8.00 D of myopia (44.5 to 71.0 micros depth, with a 5-mm diameter treatment zone). Daily confocal microscopic examinations showed acute loss of keratocytes in the anterior corneal stroma by 5 hours; losses were maximal between 24 and 48 hours for 5.00 D and 6.00 D ablations and between 72 and 96 hours for 7.00 D and 8.00 D ablations. The oval nuclei of normal keratocytes gave way to spindle-shaped fibroblasts accompanied by an accumulation of fibrillary extracellular matrix. Fibroblasts density increased toward the end of the week. Deeper ablations resulted in a longer period of keratocyte depletion and delayed onset of fibroblast activity. No epithelial, deep stromal, or endothelial abnormalities were detected, nor was stromal inflammation found. Light microscopy 1 week after PRK revealed superficial fibroplasia, which correlated with the en face images obtained with real-time in vivo confocal microscopy. The confocal microscope has a number of advantages as a clinical tool for investigation of laser-induced changes in corneal keratocytes and the stromal matrix, which may play a role in determining visual outcome after PRK.

Animals↗

Histochemical distribution of carbonic anhydrase in rat and rabbit lacrimal gland.

PURPOSE: The purpose of this study was to examine the histochemical distribution of carbonic anhydrase (CA) in lacrimal glands from rats and rabbits; and to determine if age- and/or sex-related differences exist in the amount and distribution of CA in the rat lacrimal gland. METHODS: Lacrimal glands from young (3-12 wk) and aged (2-2.5 yr), male and female F344 rats and male rabbits were fixed in 1% paraformaldehyde and embedded in glycolmethacrylate. CA histochemistry was performed on 2-microns sections. The distribution of CA activity was determined by morphometric analysis. RESULTS: In rat lacrimal gland, CA activity was distributed in a discontinuous, mosaic fashion among the acinar cells. In tissue from young males and females as well as from aged females, about 10% of the acinar tissue displayed CA activity. Significantly more activity was present in tissue from aged male rats. CA was present in the ductal lumina, suggesting that it is a secretory product of the acinar cells. In rabbits, CA activity was associated with the basolateral membranes of the terminal acinar cells only. CONCLUSIONS: In rat, the presence of CA activity in certain acinar cells and in ductal lumina suggests that CA is actively secreted by the lacrimal gland. An age-related increase in the amount of CA activity in the male glands exists that may be under gender-specific hormonal influences. In the rabbit lacrimal gland, the membrane-associated CA found uniquely with the terminal acinar cells suggests that these cells have special transport functions associated with the primary secretion of lacrimal fluid.

Animals↗

In vivo assessment of corneal stromal toxicity by tandem scanning confocal microscopy.

Epithelial wound closure following superficial corneal abrasions precipitates a complex series of cellular changes in the stroma. Transmission electron microscopy and light microscopy have demonstrated that keratocytes in the anterior stroma show prominent cytoplasmic process and granularity within an hour after this injury. Cell degeneration follows rapidly, with almost complete depletion of these keratocytes by 6-12 hours. Regeneration then occurs by 24-48 hours. These findings were confirmed in-vivo by tandem-scanning confocal light microscopy in rabbits. The optical sectioning capability of this instrument allowed us to demonstrate the three-dimensional array of fibroblast process, their subsequent condensation, and loss by sequential examinations on the same animals. Cell shrinkage and other fixation artifacts common in corneal histological sections were avoided by this technique. Using this method, we investigated the corneal cytotoxicity of an antimitotic agent, mitomycin-C and a muscarinic antagonist, atropine sulphate. Mitomycin-C, an antimetabolite used in pterygium treatment, led to irreversible keratocyte depletion even after four days of observation. However, cellular reaction to the wound were attenuated by atropine sulphate suggesting that it may be useful as a novel inhibitor of fibroblast proliferation.

Animals↗

Myopia produced in young chicks by intermittent minimal form visual deprivation--can spectacles cause myopia?

Spectacle use has been postulated to aggravate or cause human myopia. Form visual deprivation, by complete full-time occlusion or refractive lenses, has been demonstrated to cause axial myopia in animals. We raised young chicks in conditions which closely approximate plano spectacle wear in humans. In addition, we sought to achieve more physiological conditions of form deprivation. Nine newborn chicks were raised with intermittent monocular visual deprivation and their eye growth and refraction monitored by retinoscopy, ultrasonic A-scan biometry and with a travelling microscope. After hatching, the nictitating membranes were sutured for 3-4 days. This was followed by a transparent plano plastic cover over the same eye for 3-4 days per week. After 3 weeks, the manipulated eyes were more myopic (mean refraction -0.72 D, axial length 13.11 mm) than fellow eyes (+0.83 D, 11.99 mm) (p < 0.05 and p < 0.01 respectively). These results suggest that the chick eye is exquisitely sensitive to disturbances in the visual environment; intermittent minimal manipulation by conditions simulating spectacle wear in man was myopiagenic. It is postulated that spectacles can cause form visual deprivation of foveal and nonfoveal neurons (and hence myopia) by reducing luminance and contrast, chromatic and spherical aberration (in nonfoveal neurons) and restriction and distortion from the frame.

Accommodation, Ocular↗

Early diagnosis of infectious keratitis with in vivo real time confocal microscopy.

The tandem scanning confocal microscope (TSM) was adapted for in vivo examination of the cornea in rabbits with experimental bacterial and fungal keratitis. Compared to slit lamp biomicroscopy, the TSM provides superior lateral and axial resolution and serial optical sectioning capability, which may be useful for identification of corneal pathogens in the early stages of infection. We used the TSM to examine normal rabbit eyes infected with bacteria (Bacillus cereus) and a filamentous fungus (Aspergillus). We also examined a human cornea removed by penetrating keratoplasty after a clinical diagnosis of amoebic keratitis. In the early stages of bacterial infection, slit lamp examination revealed a nonspecific minimal stromal haze and limbal injection indistinguishable from sterile ulcers and epithelial defects. With the TSM, bacteria were visible as highly refractile bodies in the epithelium and superficial stroma. Branching fungal hyphae were also easily identified by the TSM, as were Acanthamoeba cysts and parasites in the subepithelial stroma. Our results indicate that this technique may provide a new modality for quickly and accurately identifying the agent of corneal infection, thereby facilitating prompt and appropriate treatment.

Acanthamoeba Keratitis↗

Effect of growth factors on collagen lattice contraction by human keratocytes.

A three-dimensional gel contraction model was used to evaluate interactions between human keratocytes and different kinds of collagen in the presence or absence of various growth factors. Bovine collagen type I or human placental copolymerized collagen type I/III was used to create the lattices. Normal keratocytes from neonatal, aged, and insulin-dependent diabetic donors, as well as abnormal keratocytes from a donor with macular corneal dystrophy, were cultured. Growth factors included epidermal growth factor (EGF), basic fibroblastic growth factor (FGF), insulin-like growth factor (IGF-I), and platelet-derived growth factor homodimer beta beta (PDGF). Gel area and optical transmittance were determined from computerized measurements. Dose-response experiments (0.01-100 ng/ml) demonstrated that PDGF at 10 ng/ml (P less than 0.005) and EGF at 1 and 10 ng/ml (P less than 0.0001) were the most effective in promoting gel contraction, compared to IGF-I and FGF. Comparison of cell strains revealed different dose-response profiles. Cells from insulin-dependent diabetics and cells from a donor with macular dystrophy contracted lattices more rapidly than cells from normal neonates (P less than 0.0001). Lattices of copolymerized human collagen type III/I demonstrated significantly reduced contraction rates (P less than 0.0001) and increased optical transmittance, compared to bovine collagen type I lattices. Ultrastructural studies revealed that keratocytes extend processes to form a network within the collagen lattice. Specialized intercellular junctional complexes were observed by transmission electron microscopy. This model provides a useful in vitro corneal stroma-equivalent for the study of keratocyte, extracellular matrix, and growth factor interactions.

Adolescent↗

EGF cell surface receptor quantitation on ocular cells by an immunocytochemical flow cytometry technique.

A method is presented for the rapid flow cytometric determination of epidermal growth factor (EGF) receptor densities on the surface of cultured ocular cells. The technique uses a biotinylated monoclonal antibody directed against the EGF receptor in conjunction with a streptavidin-bound fluorochrome and requires the specific fluorescence per cell to be measured as a function of ligand and receptor concentration. Because the measurement is noninvasive and restricted to cell surface-bound material, the cells can be kept in a physiologic environment, even at the moment of assay. Calculated receptor densities ranged from 5142/cell (infant human corneal endothelium) to 35,678/cell (infant human keratocytes) to greater than 5 x 10(5)/cell for an A431 control cell line. Species and donor age differences were noted, as was transient receptor downregulation after EGF administration. Flow cytometry represents a valuable time saving procedure for large scale applications while providing the same level of sensitivity as standard radioimmunoassays. This technique is applicable to quantitation of other growth factor cell surface receptors and could greatly expand the use of flow cytometry in the research laboratory.

Animals↗